Salvianolic Acid B Prevents Arsenic Trioxide-Induced Cardiotoxicity In Vivo and Enhances Its Anticancer Activity In Vitro

Clinical attempts to reduce the cardiotoxicity of arsenic trioxide (ATO) without compromising its anticancer activities remain to be an unresolved issue. In this study, we determined whether Sal B can protect against ATO-induced cardiac toxicity in vivo and increase the toxicity of ATO toward cancer cells. Combination treatment of Sal B and ATO was investigated using BALB/c mice and human hepatoma (HepG2) cells and human cervical cancer (HeLa) cells. The results showed that the combination treatment significantly improved the ATO-induced loss of cardiac function, attenuated damage of cardiomyocytic structure, and suppressed the ATO-induced release of cardiac enzymes into serum in BALB/c mouse models. The expression levels of Bcl-2 and p-Akt in the mice treated with ATO alone were reduced, whereas those in the mice given the combination treatment were similar to those in the control mice. Moreover, the combination treatment significantly enhanced the ATO-induced cytotoxicity and apoptosis of HepG2 cells and HeLa cells. Increases in apoptotic marker cleaved poly (ADP-ribose) polymerase and decreases in procaspase-3 expressions were observed through western blot. Taken together, these observations indicate that the combination treatment of Sal B and ATO is potentially applicable for treating cancer with reduced cardiotoxic side effects

The upper and lower solution method for nonlinear third-order three-point boundary value problem

This paper is concerned with the following nonlinear third-order three-point boundary value problem \left\{ \begin{array}{l} u^{\prime \prime \prime }(t)+f\left( t,u\left( t\right) ,u^{\prime}\left(t\right) \right) =0,\, t\in \left[ 0,1\right], \\ u\left( 0\right) =u^{\prime }\left( 0\right) =0,\, u^{\prime}\left( 1\right) =\alpha u^{\prime }\left( \eta \right),\label{1.1} \end{array} \right. where $0<\eta <1$ and $0\leq \alpha <1.$ A new maximum principle is established and some existence criteria are obtained for the above problem by using the upper and lower solution method

Linezolid and Rifampicin Combination to Combat cfr-Positive Multidrug-Resistant MRSA in Murine Models of Bacteremia and Skin and Skin Structure Infection.

Linezolid resistance mediated by the cfr gene in MRSA represents a global concern. We investigated relevant phenotype differences between cfr-positive and -negative MRSA that contribute to pathogenesis, and the efficacy of linezolid-based combination therapies in murine models of bacteremia and skin and skin structure infection (SSSI). As a group, cfr-positive MRSA exhibited significantly reduced susceptibilities to the host defense peptides tPMPs, human neutrophil peptide-1 (hNP-1), and cathelicidin LL-37 (P &lt; 0.01). In addition, increased binding to fibronectin (FN) and endothelial cells paralleled robust biofilm formation in cfr-positive vs. -negative MRSA. In vitro phenotypes of cfr-positive MRSA translated into poor outcomes of linezolid monotherapy in vivo in murine bacteremia and SSSI models. Importantly, rifampicin showed synergistic activity as a combinatorial partner with linezolid, and the EC50 of linezolid decreased 6-fold in the presence of rifampicin. Furthermore, this combination therapy displayed efficacy against cfr-positive MRSA at clinically relevant doses. Altogether, these data suggest that the use of linezolid in combination with rifampicin poses a viable therapeutic alternative for bacteremia and SSSI caused by cfr-positive multidrug resistant MRSA

Topological triply-degenerate point with double Fermi arcs

Unconventional chiral particles have recently been predicted to appear in certain three dimensional (3D) crystal structures containing three- or more-fold linear band degeneracy points (BDPs). These BDPs carry topological charges, but are distinct from the standard twofold Weyl points or fourfold Dirac points, and cannot be described in terms of an emergent relativistic field theory. Here, we report on the experimental observation of a topological threefold BDP in a 3D phononic crystal. Using direct acoustic field mapping, we demonstrate the existence of the threefold BDP in the bulk bandstructure, as well as doubled Fermi arcs of surface states consistent with a topological charge of 2. Another novel BDP, similar to a Dirac point but carrying nonzero topological charge, is connected to the threefold BDP via the doubled Fermi arcs. These findings pave the way to using these unconventional particles for exploring new emergent physical phenomena